Embolization device constructed from expansile polymer

ABSTRACT

Devices for the occlusion of body cavities, such as the embolization of vascular aneurysms and the like, and methods for making and using such devices. The devices may be comprised of novel expansile materials, novel infrastructure design, or both. The devices provided are very flexible and enable deployment with reduced or no damage to bodily tissues, conduits, cavities, etceteras.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/236,135 filed on Aug. 12, 2016 entitled Embolization DeviceConstructed from Expansile Polymer, which is a continuation of U.S.patent application Ser. No. 13/553,275 filed on Jul. 19, 2012 entitledEmbolization Device Constructed from Expansile Polymer, which is acontinuation of U.S. patent application Ser. No. 11/764,111 filed Jun.15, 2007 entitled Embolization Device Constructed From ExpansilePolymer, now U.S. Pat. No. 8,377,091, which claims the benefit of U.S.Provisional Patent Application No. 60/814,309 filed on Jun. 15, 2006entitled HESII: Embolization Device Constructed From Expansile Polymer,all of which are hereby incorporated herein in their entireties.

FIELD OF THE INVENTION

The present invention relates to devices for the occlusion of bodycavities, such as the embolization of vascular aneurysms and the like,and methods for making and using such devices.

BACKGROUND OF THE INVENTION

The occlusion of body cavities, blood vessels, and other lumina byembolization is desired in a number of clinical situations. For example,the occlusion of fallopian tubes for the purposes of sterilization, andthe occlusive repair of cardiac defects, such as a patent foramen ovale,patent ductus arteriosis, and left atrial appendage, and atrial septaldefects. The function of an occlusion device in such situations is tosubstantially block or inhibit the flow of bodily fluids into or throughthe cavity, lumen, vessel, space, or defect for the therapeutic benefitof the patient.

The embolization of blood vessels is also desired in a number ofclinical situations. For example, vascular embolization has been used tocontrol vascular bleeding, to occlude the blood supply to tumors, and toocclude vascular aneurysms, particularly intracranial aneurysms. Inrecent years, vascular embolization for the treatment of aneurysms hasreceived much attention. Several different treatment modalities havebeen shown in the prior art. One approach that has shown promise is theuse of thrombogenic microcoils. These microcoils may be made ofbiocompatible metal alloy(s) (typically a radio-opaque material such asplatinum or tungsten) or a suitable polymer. Examples of microcoils aredisclosed in the following patents: U.S. Pat. No. 4,994,069—Ritchart etal.; U.S. Pat. No. 5,133,731—Butler et al.; U.S. Pat. No. 5,226,911—Cheeet al.; U.S. Pat. No. 5,312,415—Palermo; U.S. Pat. No. 5,382,259—Phelpset al.; U.S. Pat. No. 5,382,260—Dormandy, Jr. et al.; U.S. Pat. No.5,476,472—Dormandy, Jr. et al.; U.S. Pat. No. 5,578,074—Mirigian; U.S.Pat. No. 5,582,619—Ken; U.S. Pat. No. 5,624,461—Mariant; U.S. Pat. No.5,645,558—Horton; U.S. Pat. No. 5,658,308—Snyder; and U.S. Pat. No.5,718,711—Berenstein et al; all of which are hereby incorporated byreference.

A specific type of microcoil that has achieved a measure of success isthe Guglielmi Detachable Coil (“GDC”), described in U.S. Pat. No.5,122,136—Guglielmi et al. The GDC employs a platinum wire coil fixed toa stainless steel delivery wire by a solder connection. After the coilis placed inside an aneurysm, an electrical current is applied to thedelivery wire, which electrolytically disintegrates the solder junction,thereby detaching the coil from the delivery wire. The application ofcurrent also creates a positive electrical charge on the coil, whichattracts negatively-charged blood cells, platelets, and fibrinogen,thereby increasing the thrombogenicity of the coil. Several coils ofdifferent diameters and lengths can be packed into an aneurysm until theaneurysm is completely filled. The coils thus create and hold a thrombuswithin the aneurysm, inhibiting its displacement and its fragmentation.

A more recent development in the field of microcoil vaso-occlusivedevices is exemplified in U.S. Pat. No. 6,299,619 to Greene, Jr. et al.,U.S. Pat. No. 6,602,261 to Greene, Jr. et al., and co-pending U.S.patent application Ser. No. 10/631,981 to Martinez; all assigned to theassignee of the subject invention and incorporated herein by reference.These patents disclose vaso-occlusive devices comprising a microcoilwith one or more expansile elements disposed on the outer surface of thecoil. The expansile elements may be formed of any of a number ofexpansile polymeric hydrogels, or alternatively,environmentally-sensitive polymers that expand in response to a changein an environmental parameter (e.g., temperature or pH) when exposed toa physiological environment, such as the blood stream.

This invention is a novel vaso-occlusive device, a novel expansileelement, and a combination thereof.

SUMMARY OF THE INVENTION

The present invention is directed to novel vaso-occlusive devicescomprising a carrier member, novel expansile elements, and a combinationthereof. Generally, the expansile element comprises an expansilepolymer. The carrier member may be used to assist the delivery of theexpansile element by providing a structure that, in some embodiments,allows coupling to a delivery mechanism and, in some embodiments,enhances the radiopacity of the device.

In one embodiment, the expansile polymer is an environmentally sensitivepolymeric hydrogel, such as that described in U.S. Pat. No. 6,878,384,issued Apr. 12, 2005 to Cruise et al., hereby incorporated by reference.In another embodiment, the expansile polymer is a novel hydrogelcomprised of sodium acrylate and a poly(ethylene glycol) derivative. Inanother embodiment, the expansile polymer is a hydrogel comprising aPluronics® derivative.

In one embodiment, the expansile polymer is a novel hydrogel that hasionizable functional groups and is made from macromers. The hydrogel maybe environmentally-responsive and have an unexpanded bending resistanceof from about 0.1 milligrams to about 85 milligrams. The macromers maybe non-ionic and/or ethylenically unsaturated.

In another embodiment, the macromers may have a molecular weight ofabout 400 to about 35,000, more preferably about 5,000 to about 15,000,even more preferably about 8,500 to about 12,000. In another embodiment,the hydrogel may be made of polyethers, polyurethanes, derivativesthereof, or combinations thereof. In another embodiment, the ionizablefunctional groups may comprise basic groups (e.g., amines, derivativesthereof, or combinations thereof) or acidic groups (e.g., carboxylicacids, derivatives thereof, or combinations thereof). If the ionizablefunctional groups comprise basic groups, the basic groups may bedeprotonated at pHs greater than the pKa or protonated at pHs less thanthe pKa of the basic groups. If the ionizable functional groups compriseacidic groups, the acidic groups may be protonated at pHs less than thepKa or de-protonated at pHs greater than the pKa of the acidic groups.

In another embodiment, the macromers may comprise vinyl, acrylate,acrylamide, or methacrylate derivatives of poly(ethylene glycol), orcombinations thereof. In another embodiment, the macromer may comprisepoly(ethylene glycol) di-acrylamide. In another embodiment, the hydrogelis substantially free, more preferably free of unbound acrylamide.

In another embodiment, the macromers may be cross-linked with a compoundthat contains at least two ethylenically unsaturated moities. Examplesof ethylenically unsaturated compounds includeN,N′-methylenebisacrylamide, derivatives thereof, or combinationsthereof. In another embodiment, the hydrogel may be prepared using apolymerization initiator. Examples of suitable polymerization initiatorscomprise N,N,N′,N′-tetramethylethylenediamine, ammonium persulfate,azobisisobutyronitrile, benzoyl peroxides, derivatives thereof, orcombinations thereof. The polymerization initiator may be soluble inaqueous or organic solvents. For example, azobisisobutyronitrile is notwater soluble; however, water soluble derivatives ofazobisisobutyronitrile, such as 2,2′-azobis(2-methylproprionamidine)dihydrochloride, are available. In another embodiment, the hydrogel maybe substantially non-resorbable, non-degradable or both, atphysiological conditions.

In another embodiment, the invention comprises a method for preparing anenvironmentally-responsive hydrogel for implantation in an animal. Themethod includes combining at least one, preferably non-ionic, macromerwith at least one ethylenically unsaturated moiety, at least onemacromer or monomer having at least one ionizable functional group andat least one ethylenically unsaturated moiety, at least onepolymerization initiator, and at least one solvent to form a hydrogel.The solvent may include aqueous or organic solvents, or combinationsthereof. In another embodiment, the solvent is water. Next, the hydrogelmay be treated to prepare an environmentally-responsive hydrogel,preferably one that is responsive at physiological conditions. Theionizable functional group(s) may be an acidic group (e.g., a carboxylicacid, a derivative thereof, or combinations thereof) or a basic group(e.g., an amine, derivatives thereof, or combinations thereof). If theionizable functional group comprises an acidic group, the treating stepmay comprise incubating the hydrogel in an acidic environment toprotonate the acidic groups. If the ionizable functional group comprisesa basic group, the treating step may comprise incubating the hydrogel ina basic environment to de-protonate the basic groups. In certainembodiments, it is preferable that the acidic groups are capable ofbeing de-protonated or, conversely, the basic groups are capable ofbeing protonated, after implantation in an animal.

In another embodiment, the ethylenically unsaturated macromer may have avinyl, acrylate, methacrylate, or acrylamide group; includingderivatives thereof or combinations thereof. In another embodiment, theethylenically unsaturated macromer is based upon poly(ethylene glycol),derivatives thereof, or combinations thereof. In another embodiment, theethylenically unsaturated macromer is poly(ethylene glycol)di-acrylamide, poly(ethylene glycol) di-acrylate, poly(ethylene glycol)di-methacrylate, derivatives thereof, or combinations thereof. Inanother embodiment, the ethylenically unsaturated macromer ispoly(ethylene glycol) di-acrylamide. The ethylenically unsaturatedmacromer may be used at a concentration of about 5% to about 40% byweight, more preferably about 20% to about 30% by weight. The solventmay be used at a concentration of about 20% to about 80% by weight.

In another embodiment, the combining step also includes adding at leastone cross-linking agent comprising an ethylenically unsaturatedcompound. In certain embodiments of the present invention, across-linker may not be necessary. In other words, the hydrogel may beprepared using a macromer with a plurality of ethylenically unsaturatedmoieties. In another embodiment, the polymerization initiator may be areduction-oxidation polymerization initiator. In another embodiment, thepolymerization initiator may be N,N,N′,N′-tetramethylethylenediamine,ammonium persulfate, azobisisobutyronitrile, benzoyl peroxides,2,2′-azobis(2-methylproprionamidine) dihydrochloride, derivativesthereof, or combinations thereof. In another embodiment, the combiningstep further includes adding a porosigen.

In another embodiment, the ethylenically unsaturated macromer includespoly(ethylene glycol) di-acrylamide, the macromer or monomer or polymerwith at least one ionizable group and at least one ethylenicallyunsaturated group includes sodium acrylate, the polymerization initiatorincludes ammonium persulfate and N,N,N,′,N′ tetramethylethylenediamine,and the solvent includes water.

In another embodiment, the ethylenically unsaturated macromer has amolecular weight of about 400 to about 35,000 grams/mole, morepreferably about 2,000 to about 25,000 grams/mole, even more preferablyabout 5,000 to about 15,000 grams/mole, even more preferably about 8,000to about 12,500 grams/mole, and even more preferably about 8,500 toabout 12,000 grams/mole. In another embodiment, theenvironmentally-responsive hydrogel is substantially non-resorbable, ornon-degradable or both at physiological conditions. In certainembodiments, the environmentally-responsive hydrogel may besubstantially free or completely free of unbound acrylamide.

In one embodiment, the carrier member comprises a coil or microcoil madefrom metal, plastic, or similar materials. In another embodiment, thecarrier member comprises a braid or knit made from metal, plastic, orsimilar materials. In another embodiment, the carrier member comprises aplastic or metal tube with multiple cuts or grooves cut into the tube.

In one embodiment, the expansile element is arranged generallyco-axially within the carrier member. In another embodiment, a stretchresistant member is arranged parallel to the expansile element. Inanother embodiment, the stretch resistant member is wrapped, tied, ortwisted around the expansile element. In another embodiment, the stretchresistant member is positioned within the expansile element.

In one embodiment, the device comprising the expansile element andcarrier member are detachably coupled to a delivery system. In anotherembodiment, the device is configured for delivery by pushing orinjecting through a conduit into a body.

In one embodiment, the expansile element is environmentally sensitiveand exhibits delayed expansion when exposed to bodily fluids. In anotherembodiment, the expansile element expands quickly upon contact with abodily fluid. In another embodiment, the expansile element comprises aporous or reticulated structure that may form a surface or scaffold forcellular growth.

In one embodiment, the expansile element expands to a dimension that islarger than the diameter of the carrier member in order to provideenhanced filling of the lesion. In another embodiment, the expansileelement expands to a dimension equal to or smaller than the diameter ofthe carrier member to provide a scaffold for cellular growth, release oftherapeutic agents such as pharmaceuticals, proteins, genes, biologiccompounds such as fibrin, or the like.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing one embodiment of the presentinvention prior to expansion of the expansile element;

FIG. 2 is a perspective view showing a device similar to FIG. 1 in anexpanded state;

FIG. 3 is a perspective view of an alternative embodiment of the presentinvention;

FIG. 4 is a perspective view of an alternative embodiment wherein thecarrier member comprises a fenestrated tube, braid or knit;

FIG. 5 is a perspective view of an alternative embodiment incorporatinga stretch resistant member running approximately parallel to theexpansile element;

FIG. 6 is a perspective view of an alternative embodiment incorporatinga stretch resistant member approximately intertwined with the expansileelement;

FIG. 7 is a perspective view of an alternative embodiment wherein theexpansile element has formed a loop or fold outside the carrier member.

FIG. 8 is a perspective view of an alternative embodiment showing adevice similar to those shown in FIG. 1 and FIG. 2 wherein the expansileelement is not expanded to a diameter larger than the carrier member.

DESCRIPTION OF THE INVENTION

As used herein, the term “macromer” refers to a large moleculecontaining at least one active polymerization site or binding site.Macromers have a larger molecular weight than monomers. For example, anacrylamide monomer has a molecular weight of about 71.08 grams/molewhereas a poly(ethylene glycol) di-acrylamide macromer may have amolecular weight of about 400 grams/mole or greater. Preferred macromersare non-ionic, i.e. they are uncharged at all pHs.

As used herein, the term “environmentally responsive” refers to amaterial (e.g., a hydrogel) that is sensitive to changes in environmentincluding but not limited to pH, temperature, and pressure. Many of theexpansile materials suitable for use in the present invention areenvironmentally responsive at physiological conditions.

As used herein, the term “non-resorbable” refers to a material (e.g., ahydrogel) that cannot be readily and/or substantially degraded and/orabsorbed by bodily tissues.

As used herein, the term “unexpanded” refers to the state at which ahydrogel is substantially not hydrated and, therefore, not expanded.

As used herein, the term “ethylenically unsaturated” refers to achemical entity (e.g., a macromer, monomer or polymer) containing atleast one carbon-carbon double bond.

As used herein, the term “bending resistance” refers to the resistanceexhibited by a sample (e.g., an unexpanded hydrogel) as it steadily andevenly is moved across a resistance-providing arm or vane. The maximumdisplacement of the resistance-providing arm or vane is measured at thepoint the sample bends and releases the resistance-providing arm orvane. That maximum displacement is converted to bending “resistance” or“stiffness” using conversions appropriate to the machine, itscalibration, and the amount of resistance (e.g., weight), if any,associated with the resistance-providing arm or vane. Herein, the unitsof measure for bending resistance will be milligrams (mg) andessentially is the amount of force required to bend the sample.

Referring to FIG. 1-8, the invention is a device comprising an expansileelement 1 and a carrier member 2. The expansile element 1 may be madefrom a variety of suitable biocompatible polymers. In one embodiment,the expansile element 1 is made of a bioabsorbable or biodegradablepolymer, such as those described in U.S. Pat. Nos. 7,070,607 and6,684,884, the disclosures of which are incorporated herein byreference. In another embodiment, the expansile element 1 is made of asoft conformal material, and more preferably of an expansile materialsuch as a hydrogel.

In one embodiment, the material forming the expansile element 1 is anenvironmentally responsive hydrogel, such as that described in U.S. Pat.No. 6,878,384, the disclosure of which is incorporated herein byreference. Specifically, the hydrogels described in U.S. Pat. No.6,878,384 are of a type that undergoes controlled volumetric expansionin response to changes in such environmental parameters as pH ortemperature. These hydrogels are prepared by forming a liquid mixturethat contains (a) at least one monomer and/or polymer, at least aportion of which is sensitive to changes in an environmental parameter;(b) a cross-linking agent; and (c) a polymerization initiator. Ifdesired, a porosigen (e.g., NaCl, ice crystals, or sucrose) may be addedto the mixture, and then removed from the resultant solid hydrogel toprovide a hydrogel with sufficient porosity to permit cellular ingrowth.The controlled rate of expansion is provided through the incorporationof ethylenically unsaturated monomers with ionizable functional groups(e.g., amines, carboxylic acids). For example, if acrylic acid isincorporated into the crosslinked network, the hydrogel is incubated ina low pH solution to protonate the carboxylic acid groups. After theexcess low pH solution is rinsed away and the hydrogel dried, thehydrogel can be introduced through a microcatheter filled with saline atphysiological pH or with blood. The hydrogel cannot expand until thecarboxylic acid groups deprotonate. Conversely, if an amine-containingmonomer is incorporated into the crosslinked network, the hydrogel isincubated in a high pH solution to deprotonate amines. After the excesshigh pH solution is rinsed away and the hydrogel dried, the hydrogel canbe introduced through a microcatheter filled with saline atphysiological pH or with blood. The hydrogel cannot expand until theamine groups protonate.

In another embodiment, the material forming the expansile element 1 ismay be an environmentally responsive hydrogel, similar to thosedescribed in U.S. Pat. No. 6,878,384; however, an ethylenicallyunsaturated, and preferably non-ionic, macromer replaces or augments atleast one monomer or polymer. The Applicants surprisingly havediscovered that hydrogels prepared in accordance with this embodimentcan be softer and/or more flexible in their unexpanded state than thoseprepared in accordance with U.S. Pat. No. 6,878,384. Indeed, hydrogelsprepared in accordance with this embodiment may have an unexpandedbending resistance of from about 0.1 mg to about 85 mg, about 0.1 mg toabout 50 mg, about 0.1 mg to about 25 mg, about 0.5 mg to about 10 mg,or about 0.5 mg to about 5 mg. The Applicants also have discovered thatethylenically unsaturated and non-ionic macromers (e.g., poly(ethyleneglycol) and derivatives thereof) may be used not only to prepare asofter unexpanded hydrogel; but, in combination with monomers orpolymers containing ionizable groups, one that also may be treated to bemade environmentally responsive. The surprising increase in unexpandedflexibility enables the hydrogels to be, for example, more easilydeployed in an animal or deployed with reduced or no damage to bodilytissues, conduits, cavities, etceteras.

The hydrogels prepared from non-ionic macromers in combination withmonomers or polymers with ionizable functional groups still are capableof undergoing controlled volumetric expansion in response to changes inenvironmental parameters. These hydrogels may be prepared by combiningin the presence of a solvent: (a) at least one, preferably non-ionic,macromer with a plurality of ethylenically unsaturated moieties; (b) amacromer or polymer or monomer having at least one ionizable functionalgroup and at least one ethylenically unsaturated moiety; and (c) apolymerization initiator. It is worthwhile to note that with this typeof hydrogel, a cross-linking agent may not be necessary forcross-linking since, in certain embodiments, the components selected maybe sufficient to form the hydrogel. As hereinbefore described, aporosigen may be added to the mixture and then removed from theresultant hydrogel to provide a hydrogel with sufficient porosity topermit cellular ingrowth.

The non-ionic macromer-containing hydrogels' controlled rate ofexpansion may be provided through the incorporation of at least onemacromer or polymer or monomer having at least one ionizable functionalgroup (e.g., amine, carboxylic acid). As discussed above, if thefunctional group is an acid, the hydrogel is incubated in a low pHsolution to protonate the group. After the excess low pH solution isrinsed away and the hydrogel dried, the hydrogel can be introducedthrough a microcatheter, preferably filled with saline. The hydrogelcannot expand until the acid group(s) deprotonates. Conversely, if thefunctional group is an amine, the hydrogel is incubated in a high pHsolution to deprotonate the group. After the excess high pH solution isrinsed away and the hydrogel dried, the hydrogel can be introducedthrough a microcatheter, preferably filled with saline. The hydrogelcannot expand until the amine(s) protonates.

More specifically, in one embodiment, the hydrogel is prepared bycombining at least one non-ionic macromer having at least oneunsaturated moiety, at least one macromer or monomer or polymer havingat least one ionizable functional group and at least one ethylenicallyunsaturated moiety, at least one polymerization initiator, and asolvent. Optionally, an ethylenically unsaturated crosslinking agentand/or a porosigen also may be incorporated. Preferred concentrations ofthe non-ionic macromers in the solvent range from about 5% to about 40%(w/w), more preferably about 20% to about 30% (w/w). A preferrednon-ionic macromer is poly(ethylene glycol), its derivatives, andcombinations thereof. Derivatives include, but are not limited to,poly(ethylene glycol) di-acrylamide, poly(ethylene glycol) di-acrylate,and poly(ethylene glycol) dimethacrylate. Poly(ethylene glycol)di-acrylamide is a preferred derivative of poly(ethylene glycol) and hasa molecular weight ranging from about 8,500 to about 12,000. Themacromer may have less than 20 polymerization sites, more preferablyless than 10 polymerization sites, more preferably about five or lesspolymerization sites, and more preferably from about two to about fourpolymerization sites. Poly(ethylene glycol) di-acrylamide has twopolymerization sites.

Preferred macromers or polymers or monomers having at least oneionizable functional group include, but are not limited to compoundshaving carboxylic acid or amino moieties or, derivatives thereof, orcombinations thereof. Sodium acrylate is a preferred ionizablefunctional group-containing compound and has a molecular weight of 94.04g/mole. Preferred concentrations of the ionizable macromers or polymersor monomers in the solvent range from about 5% to about 40% (w/w), morepreferably about 20% to about 30% (w/w). At least a portion, preferablyabout 10%-50%, and more preferably about 10%-30%, of the ionizablemacromers or polymers or monomers selected should be pH sensitive. It ispreferred that no free acrylamide is used in the macromer-containinghydrogels of the present invention.

When used, the crosslinking agent may be any multifunctionalethylenically unsaturated compound, preferably N,N′-methylenebisacrylamide. If biodegradation of the hydrogel material isdesired, a biodegradable crosslinking agent may be selected. Theconcentrations of the crosslinking agent in the solvent should be lessthan about 1% w/w, and preferably less than about 0.1% (w/w).

As described above, if a solvent is added, it may be selected based onthe solubilities of the macromer(s) or monomer(s) or polymer(s),crosslinking agent, and/or porosigen used. If a liquid macromer ormonomer or polymer solution is used, a solvent may not be necessary. Apreferred solvent is water, but a variety of aqueous and organicsolvents may be used. Preferred concentrations of the solvent range fromabout 20% to about 80% (w/w), more preferably about 50% to about 80%(w/w).

Crosslink density may be manipulated through changes in the macromer ormonomer or polymer concentration, macromer molecular weight, solventconcentration and, when used, crosslinking agent concentration. Asdescribed above, the hydrogel may be crosslinked viareduction-oxidation, radiation, and/or heat. A preferred type ofpolymerization initiator is one that acts via reduction-oxidation.Suitable polymerization initiators include, but are not limited to,N,N,N′,N′-tetramethylethylenediamine, ammonium persulfate,azobisisobutyronitrile, benzoyl peroxides,2,2′-azobis(2-methylpropionamidine) dihydrochloride, derivativesthereof, or combinations thereof. A combination of ammonium persulfateand N,N,N′,N′-tetramethylethylenediamine is a preferred polymerizationinitiator for use in the macromer containing embodiments of theinvention.

After polymerization is complete, the hydrogels of the present inventionmay be washed with water, alcohol or other suitable washing solution(s)to remove any porosigen(s), any unreacted, residual macromer(s),monomer(s), and polymer(s) and any unincorporated oligomers. Preferablythis is accomplished by initially washing the hydrogel in distilledwater.

The hydrogels of the present invention may be madeenvironmentally-responsive by protonating or deprotonating the ionizablefunctional groups present on the hydrogel network, as discussed above.Once the hydrogel has been prepared and, if needed, washed, the hydrogelmay be treated to make the hydrogel environmentally-responsive. Forhydrogel networks where the ionizable functional groups are carboxylicacid groups, the hydrogel is incubated in a low pH solution. The freeprotons in the solution protonate the carboxylic acid groups on thehydrogel network. The duration and temperature of the incubation and thepH of the solution influence the amount of control on the expansionrate. In general, the duration and temperature of the incubation aredirectly proportional to the amount of expansion control, while theincubation solution pH is inversely proportional thereto.

It has been determined that incubation solution water content alsoaffects expansion control. In this regard, higher water content enablesgreater hydrogel expansion and is thought to increase the number ofprotonation-accessible carboxylic acid groups. An optimization of watercontent and pH is required for maximum control on expansion rate.Expansion control, among other things, has an effect on devicepositioning/repositioning time. Typically, a positioning/repositioningtime of about 0.1 to about 30 minutes is preferred for hydrogel devicesin accordance with the present invention.

After incubation, the excess treating solution is washed away and thehydrogel material is dried. A hydrogel treated with the low pH solutionhas been observed to dry down to a smaller dimension than an untreatedhydrogel. This effect is desirable since devices containing thesehydrogels may be delivered through a microcatheter.

For hydrogel networks where the ionizable functional groups are aminegroups, the hydrogel is incubated in a high pH solution. Unlikecarboxylic acid functional groups, deprotonation occurs on the aminegroups of the hydrogel network at high pH. Aside from incubationsolution pH, the incubation is carried out similarly to that of thecarboxylic acid containing hydrogels. In other words, the duration andtemperature of the incubation and the pH of the solution are directlyproportional to the amount of expansion control. After incubation isconcluded, the excess treating solution is washed away and the hydrogelmaterial is dried.

In a preferred embodiment, the expansile element 1 is an expansilehydrogel comprised of (a) at least one, preferably non-ionic,ethylenically unsaturated macromer or monomer or polymer having at leasttwo crosslinkable groups; (b) at least one monomer and/or polymer whichhas at least one crosslinkable groups, and at least one moiety that issensitive to changes in an environmental parameter; and (c) apolymerization initiator. In some embodiments, the monomers and polymersmay be water soluble, while in other embodiments they may be non-watersoluble. Suitable polymers for components (a) and (b) includepoly(ethylene glycol), poly(ethylyene oxide), poly(vinyl alcohol),poly(propylene oxide), poly(propylene glycol), poly(ethyleneoxide)-co-poly(propylene oxide), poly(vinyl pyrrolidinone), poly(aminoacids), dextrans, poly(ethyloxazoline), polysaccharides, proteins,glycosaminoglycans, and carbohydrates, and derivatives thereof. Thepreferred polymer is poly(ethylene glycol) (PEG), especially forcomponent (a). Alternatively, polymers that biodegrade partly orcompletely may be utilized.

One embodiment comprises combining in the presence of a solvent (a)about 5% to about 40% of a non-ionic, ethylenically unsaturated macromeror monomer or polymer; (b) about 5% to about 40% of an ethylenicallyunsaturated monomer or polymer with at least one ionizable functionalgroup; and, (c) a polymerization initiator. Suitable ionizable,ethylenically unsaturated monomers include acrylic acid and methacrylicacid, as well as derivatives thereof. One suitable monomer having atleast one ionizable functional group is sodium acrylate. Suitablemacromers with two ethylenically unsaturated moities includepoly(ethylene glycol) di-acrylate and poly(ethylene glycol)di-acrylamide, and poly(ethylene glycol) di-acrylamide, which havemolecular weights ranging between 400 and 30,000 grams/mole. The use ofmacromers with a plurality of ethylenically unsaturated groups permitsthe elimination of the crosslinker, as the crosslinker functions areperformed by the multi-functional polymer. In one embodiment, thehydrogel comprises, about 5% to about 40% sodium acrylate, about 5% toabout 40% poly(ethylene glycol) di-acrylamide, and the remaining amountwater.

A sodium acrylate/poly(ethylene glycol) di-acrylamide hydrogel is usedto enhance the mechanical properties of the previously-describedenvironmentally responsive hydrogel. Since a sodiumacrylate/poly(ethylene glycol) di-acrylamide hydrogel is softer than asodium acrylate/acrylamide hydrogel (e.g., the one utilized in HydrogelEmbolic System (HES) made by MicroVention, Aliso Viejo, Calif.), devicesincorporating it may be more flexible. Due to the relative stiffness ofthe HES, MicroVention recommends pre-softening the device by soaking inwarm fluid or steaming the implant. In addition, devices made fromacrylamide are relatively straight before pre-softening because thestiffness of the acrylamide-based hydrogel prevents the carrier member(for the HES, a microcoil) from assuming its secondary configuration.Devices made from a sodium acrylate/poly(ethylene glycol) di-acrylamidehydrogel may not require pre-softening techniques such as soaking inwarm fluid such as saline or blood or exposure to steam in order to forminto a secondary configuration heat-set into the carrier member 2 or asimilar carrier member. Thus, in embodiments comprising, for example,sodium acrylate and poly(ethylene glycol) di-acrylamide, a substantiallycontinuous length of hydrogel disposed either within the lumen 3 of thecarrier member 2 as shown in, for example, FIG. 1 or on a carrierelement such as those shown in the Martinez '981 application or Greene'261, will form into the secondary configuration pre-formed into thecarrier member without pre-treatment (e.g. exposure to steam, fluid, orblood). This makes the device easier to use because it allowselimination of the pre-treatment step and the device may be safer whendeployed into the patient because a softer device is less likely tocause damage to the lesion.

EXAMPLE

3 g of acrylamide, 1.7 g of acrylic acid, 9 mg of bisacrylamide, 50 mgof N,N,N′,N′-tetramethylethylenediamine, 15 mg of ammonium persulfate,and 15.9 g water were combined and polymerized in a 0.020 inch tube. Thetubularized polymer was removed from the tubing to prepare Hydrogel 1 inaccordance with U.S. Pat. No. 6,878,384.

4.6 g of poly(ethylene glycol) diacrylamide, 3.3 g of sodium acrylate,100 mg of N,N,N′,N′-tetramethylethylenediamine, 25 mg of ammoniumpersulfate, and 15.9 g water were combined and polymerized in a 0.020inch tube. The tubularized polymer was removed from the tubing toprepare Hydrogel 2, in accordance with a macromer-containing hydrogelembodiment of the present invention.

A hydrogel identical to Hydrogel 2 was prepared; however, itadditionally was acid treated in accordance with the present inventionto prepare Hydrogel 2-Acid.

A large platinum microcoil has a 0.014 inch outer diameter and a 0.0025inch filar. A small platinum microcoil has a 0.010 inch outer diameterand a 0.002 inch filar.

The bending resistance of the unexpanded hydrogel samples and thebending resistance of the microcoils were obtained using a Gurley 4171ETtubular sample stiffness tester with a 5-gram counterweight attached toits measuring vane. The sample length was 1 inch. The average measuredresistance and standard deviation of five replicates each are summarizedin the following table.

MEASURED RESISTANCE, SAMPLE milligrams Hydrogel 1 88 ± 13 Hydrogel 2 23± 1  Hydrogel 2-Acid 1 ± 0 Large Platinum Coil 5 ± 1 Small Platinum Coil2 ± 1

The results show the large difference in relative stiffness between thefirst generation Hydrogel 1 (HES), the second generationmacromer-containing Hydrogel 2, the second generationmacromer-containing Hydrogel 2 that has been acid treated, and themicrocoils. Hydrogel 1 is nearly 20 times stiffer than a large platinummicrocoil whereas Hydrogel 2 is less than 5 times stiffer than a largeplatinum microcoil. The acid-treated Hydrogel 2 is less stiff than alarge platinum microcoil and about as stiff as a small platinummicrocoil. A skilled artisan will appreciate that much more flexibleunexpanded macromer-containing hydrogels are provided by the methods andmaterials disclosed in the present invention. When used in a medicaldevice, these hydrogels may result in a more flexible medical device aswell.

In another embodiment, monomers are used to impart moieties to theexpansile element 1 that are suitable for coupling bioactive compounds,for example anti-inflammatory agents such as corticosteroids (e.g.prednisone and dexamethasone); or vasodilators such as nitrous oxide orhydralazine; or anti-thrombotic agents such as aspirin and heparin; orother therapeutic compounds, proteins such as mussel adhesive proteins(MAPs), amino acids such as 3-(3,4-dihydroxyphenyl)-L-alanine (DOPA),genes, or cellular material; see U.S. Pat. No. 5,658,308, WO 99/65401,Polymer Preprints 2001, 42(2), 147 Synthesis and Characterization ofSelf-Assembling Block Copolymers Containing Adhesive Moieties by KuiHwang et. al., and WO 00/27445; the disclosures of which are herebyincorporated by reference. Examples of moieties for incorporation intohydrogel materials include, but are not limited to, hydroxyl groups,amines, and carboxylic acids.

In another embodiment, the expansile element 1 may be renderedradiopaque by incorporation of monomers and/or polymers containing, forexample, iodine, or the incorporation of radiopaque metals such astantalum and platinum.

In some embodiments, the carrier member 2 is a flexible, elongatestructure. Suitable configurations for the carrier member 2 includehelical coils, braids, and slotted or spiral-cut tubes. The carriermember 2 may be made of any suitable biocompatible metal or polymer suchas platinum, tungsten, PET, PEEK, Teflon, Nitinol, Nylon, steel, and thelike. The carrier member may be formed into a secondary configurationsuch as helix, box, sphere, flat rings, J-shape, S-shape or othercomplex shape known in the art. Examples of appropriate shapes aredisclosed in Horton U.S. Pat. No. 5,766,219; Schaefer application Ser.No. 10/043,947; and Wallace U.S. Pat. No. 6,860,893; all herebyincorporated by reference.

As previously described, some embodiments of the instant invention maycomprise polymers that are sufficiently soft and flexible that asubstantially continuous length of the expansile element 1 will forminto a secondary configuration similar to the configuration originallyset into the carrier member 2 without pre-softening the device orexposing it to blood, fluid, or steam.

In some embodiments, the carrier member 2 incorporates at least one gap7 that is dimensioned to allow the expansile element 1 to expand throughthe gap (one embodiment of this configuration is shown in FIGS. 1-2). Inother embodiments, the carrier member 2 incorporates at least one gap 7that allows the expansile element 1 to be exposed to bodily fluids, butthe expansile element 1 does not necessarily expand through the gap (oneembodiment of this configuration is shown in FIG. 8). In otherembodiments, no substantial gap is incorporated into the carrier member2. Rather, fluid is allowed to infiltrate through the ends of the deviceor is injected through a lumen within the delivery system and theexpansile element 1 expands and forces its way through the carriermember 2.

In one embodiment shown in FIG. 1, the expansile element 1 comprises anacrylamide or poly(ethylene glycol)-based expansile hydrogel. Thecarrier member 2 comprises a coil. At least one gap 7 is formed in thecarrier member 2. The expansile element 1 is disposed within the lumen 3defined by the carrier member 2 in a generally coaxial configuration. Atip 4 is formed at the distal end of the device 11 by, for example, alaser, solder, adhesive, or melting the hydrogel material itself. Theexpansile element 1 may run continuously from the proximal end to thedistal end, or it may run for a portion of the device then terminatebefore reaching the distal or proximal end, or both.

As an example, in one embodiment the device is dimensioned to treat acerebral aneurysm. Those skilled in the art will appreciate that thedimensions used in this example could be re-scaled to treat larger orsmaller lesions. In this embodiment, the expansile element 1 is about0.001″-0.030″ before expansion and about 0.002″-0.25″ after expansion.The expansile element is, for example, approximately 5%-30% sodiumacrylate, 10%-30% poly(ethylene glycol) di-acrylamide with a molecularweight ranging between 400 and 30,000 grams/mole, and the remainderwater. Those skilled in the art will appreciate that the ratio ofexpansion could be controlled by changing the relative amounts of sodiumacrylate, PEG di-acrylamide, and water. The carrier member 2 in thisembodiment is a microcoil in the range of about 0.005″-0.035″ indiameter. In an alternate embodiment, the microcoil diameter has a rangeof 0.008′-0.016′. The microcoil may have a filar in the range of0.0005″-0.01″. In an alternate embodiment, the filar range is0.00075″-0.004″. The implant 11 comprises at least one gap 7 rangingfrom 0.5 filars (0.00025″) long to 20 filars (0.2″) long. In analternate embodiment, the gap range is between approximately 0.00025″ to0.005″. In one preferred embodiment, the microcoil has a diameter of0.012″ and a 0.002″ filar, with a gap 7 of 0.0013″. A coupler 13 isplaced near the proximal end to allow the implant 11 to be detachablycoupled to a delivery system or pushed or injected through a catheter.Examples of delivery systems are found in co-pending application Ser.No. 11/212,830 to Fitz, U.S. Pat. No. 6,425,893 to Guglielmi, U.S. Pat.No. 4,994,069 to Ritchart, U.S. Pat. No. 6,063,100 to Diaz, and U.S.Pat. No. 5,690,666 to Berenstein; the disclosures of which are herebyincorporated by reference.

In this embodiment, the implant 11 is constructed by formulating andmixing the hydrogel material as previously described in order to formthe expansile element 1. The carrier member 2 is wound around a helicalor complex form, and then heat-set by techniques known in the art toform a secondary diameter ranging from 0.5 mm to 30 mm and a lengthranging from 5 mm to 100 cm. After processing, washing, and optionalacid treatment, the expansile element 1 is threaded through the lumen 3of the carrier member 2. The distal end of the expansile element 1 isthen tied, for example by forming a knot, to the distal end of thecarrier member 2. Adhesive, such as UV curable adhesive or epoxy, may beused to further enhance the bond between the expansile element 1 and thecarrier member 2 and to form the distal tip 4. Alternatively, the tipmay be formed by, for example, a laser weld or solder ball.

In some embodiments, depending on the size of the gap 7 and the ratio ofexpansion, loops or folds 12 may form as shown in FIG. 7 as theexpansile element 1 expands. Although the loop or fold 12 may not affectthe functionality of the device, in some embodiments it is desirable toprevent the loop or fold 12 from forming. This can be done by stretchingthe expansile element 1 either before placing it within the carriermember 2 or after the distal end of the expansile element 1 is securedto the carrier member 2. For example, once the distal end of theexpansile element 1 is secured to the carrier member 2, the expansileelement 1 is stretched to a final length between 101% to 1000% of itsinitial length (e.g. if the initial length is 1″, the expansile elementis stretched to 1.01″-10.0″) or to a length sufficient to prevent loopsfrom forming in the expansile element 1 after expansion. For example, inthe previously described cerebral aneurysm treatment embodiment, theexpansile element 1 is stretched to a final length, which isapproximately 125%-600% of the initial length. In an alternateembodiment, the expansile element 1 is stretched to a final length,which is approximately 125%-300% of the initial length. In one preferredembodiment the expansile element is stretched to a final length that isapproximately 267% of its initial length. After stretching, theexpansile element 1 may be trimmed to match the length of the carriermember 2 and then bonded near the proximal end of the carrier member 2by, for example, tying a knot, adhesive bonding, or other techniquesknown in the art.

Once the implant 11 has been constructed, it is attached to a deliverysystem previously described by methods known in the art. The device mayalso be exposed to, for example, e-beam or gamma radiation to cross-linkthe expansile element 1 and to control its expansion. This is describedin U.S. Pat. No. 6,537,569 which is assigned to the assignee of thisapplication and hereby incorporated by reference.

Previously, the secondary dimensions of prior devices (e.g. HES) aregenerally sized to a dimension 1-2 mm smaller than the dimension (i.e.volume) of the treatment site due to the relative stiffness of thesedevices. The increased flexibility and overall design of the implant 11of the instant invention allows the secondary shape of the implant 11 tobe sized to a dimension approximately the same size as the treatmentsite, or even somewhat larger. This sizing further minimizes the risk ofthe implant moving in or slipping out of the treatment site.

Prior implant devices, such as the HES device, currently provide theuser with about 5 minutes of repositioning time. However, the implant 11of the present invention increases the length of repositioning time. Insome embodiments, the repositioning time during a procedure can beincreased to about 30 minutes. In this respect, the user is providedwith a longer repositioning time to better achieve a desired implantconfiguration

FIG. 2 shows an implant 11 similar to that shown in FIG. 1 after theexpansile element 1 has expanded through the gap 7 to a dimension largerthan the carrier member 2.

FIG. 3 shows an implant 11 wherein multiple expansile elements 1 runsomewhat parallel to each other through the carrier member 2. In oneembodiment, this configuration is constructed by looping a singleexpansile element 1 around the tip 4 of the implant 11 and tying bothends of the expansile element 1 to the proximal end of the carriermember 2. In another embodiment, multiple strands of the expansileelement 1 may be bonded along the length of the carrier member 2. Theconstruction of these embodiments may also comprise stretching theexpansile element 1 as previously described and/or forming gaps in thecarrier member 2.

FIG. 4 shows an embodiment wherein the implant 11 comprises a non-coilcarrier member 2. In one embodiment, the carrier member 2 is formed bycutting a tube or sheet of plastic such as polyimide, nylon, polyester,polyglycolic acid, polylactic acid, PEEK, Teflon, carbon fiber orpyrolytic carbon, silicone, or other polymers known in the art with, forexample; a cutting blade, laser, or water jet in order to form slots,holes, or other fenestrations through which the expansile element 1 maybe in contact with bodily fluids. The plastic in this embodiment mayalso comprise a radiopaque agent such as tungsten powder, iodine, orbarium sulfate. In another embodiment, the carrier member 2 is formed bycutting a tube or sheet of metal such as platinum, steel, tungsten,Nitinol, tantalum, titanium, chromium-cobalt alloy, or the like with,for example; acid etching, laser, water jet, or other techniques knownin the art. In another embodiment, the carrier member 2 is formed bybraiding, knitting, or wrapping metallic or plastic fibers in order toform fenestrations.

FIG. 5 shows an implant 11 comprising a carrier member 2, an expansileelement 1, and a stretch resistant member 10. The stretch resistantmember 10 is used to prevent the carrier member 2 from stretching orunwinding during delivery and repositioning. The stretch resistantmember 10 may be made from a variety of metallic or plastic fibers suchas steel, Nitinol, PET, PEEK, Nylon, Teflon, polyethylene, polyolefin,polyolefin elastomer, polypropylene, polylactic acid, polyglycolic acid,and various other suture materials known in the art. Construction of theimplant 11 may be by attaching the ends of the stretch resistant member10 to the ends of the carrier member 2 as described by U.S. Pat. No.6,013,084 to Ken and U.S. Pat. No. 5,217,484 to Marks both herebyincorporated by reference. Alternatively, the distal end of the stretchresistant member 10 may be attached near the distal end of the carriermember 2 and the proximal end to the stretch resistant member 10attached to the delivery system as described in co-pending applicationSer. No. 11/212,830 to Fitz.

FIG. 6 is an alternative embodiment comprising a stretch resistantmember 10 wrapped around, tied to, or intertwined with the expansileelement 1. This may occur over the length of the expansile element 1, orthe wrapping or tying may be in only one area to facilitate bonding theexpansile element 1 to the carrier element 2 by using the stretchresistant member 10 as a bonding element.

FIG. 7 shows a loop or fold 12 of the expansile element 1 protrudingoutside the carrier element 2. In some embodiments, it may be desirableto avoid this condition by, for example, stretching the expansileelement 1 as previously described. This would be done, for example, inembodiments configured for delivery through a small microcatheter toprevent the implant 11 from becoming stuck in the microcatheter duringdelivery. In other embodiments, slack may be added to the expansileelement 1 so that the loop or fold will be pre-formed into the implant11. This would be done in embodiments where, for example, a large amountof volumetric filling were necessary because the loops or folds wouldtend to increase the total length of the expansile element 1.

FIG. 8 shows an embodiment wherein the expansile element 1 is configuredto expand to a dimension larger than its initial dimension, but smallerthan the outer dimension of the carrier member 2. This may be done byadjusting the ratio of, for example, PEG di-acrylamide to sodiumacrylate in embodiments wherein the expansile element 1 comprises ahydrogel. Alternatively, a relatively high dose of radiation could beused to cross-link the expansile element 1, thus limiting its expansion.Embodiments such as shown in FIG. 8 are desirable when low volumetricfilling is necessary and it is desirable to have a substrate for tissuegrowth and proliferation that the expansile element 1 provides. In anembodiment used to treat cerebral aneurysms, this configuration would beused as a final or “finishing” coil, or in devices dimensioned to treatsmall (under 10 mm diameter) aneurysms, or as a first “framing” or 3-Dcoil placed. In one embodiment, the expansile element 1 comprises ahydrogel incorporating a porosigen as previously described to provide areticulated matrix to encourage cell growth and healing. Incorporating,for example, growth hormones or proteins in the expansile element 1 aspreviously described may further enhance the ability of the implant 11to elicit a biological response.

In one embodiment of the invention a vaso-occlusive device comprises anexpansile polymer element having an outer surface, a carrier member thatcovers at least a portion of the outer surface of the expansile polymerelement, and wherein no carrier is disposed within the outer surface ofthe expansile element.

In another embodiment, a vaso-occlusive device comprises a coil having alumen and a hydrogel polymer having an outer surface wherein thehydrogel polymer is disposed within the lumen of the coil and whereinthe hydrogel polymer does not contain a coil within the outer surface ofthe hydrogel polymer.

In another embodiment, a vaso-occlusive device comprises a carriermember formed into a secondary configuration and an expansile element,wherein the expansile element is made from a polymer formulated to havesufficient softness that the expansile element will substantially takethe shape of the secondary configuration formed into the carrier memberwithout pre-treatment.

In another embodiment, a vaso-occlusive device comprises a carriermember formed into a secondary configuration and a substantiallycontinuous length of hydrogel, wherein the device will substantiallytake the shape of the secondary configuration formed into the carriermember without pre-treatment.

In another embodiment, a vaso-occlusive device comprises a microcoilhaving an inner lumen and an expansile element disposed within the innerlumen. In this embodiment the expansile element comprises a hydrogelselected from the group consisting of acrylamide, poly(ethylene glycol),Pluronic, and poly(propylene oxide).

In another embodiment, a vaso-occlusive device comprises a coil and ahydrogel polymer disposed at least partially within the coil wherein thehydrogel has an initial length and wherein the hydrogel polymer has beenstretched to a second length that is longer than the initial length.

In another embodiment, a vaso-occlusive device comprises an expansileelement and a carrier member defining an inner lumen, wherein theexpansile element is disposed within the inner lumen of the carriermember and wherein the expansile element has been stretched to a lengthsufficient to prevent a loop of the expansile element from protrudingthrough the carrier member.

The invention disclosed herein also includes a method of manufacturing amedical device. The method comprises providing a carrier member havingan inner lumen and an expansile element, inserting the expansile elementinto the inner lumen of the carrier member, and stretching the expansileelement.

In another embodiment, a vaso-occlusive device comprises an expansileelement encapsulated by a carrier element, wherein said expansileelement is comprised substantially entirely and substantially uniformlyof material having an expansile property.

In another embodiment, a vaso-occlusive device comprises a carrierelement and an expansile element wherein the carrier element has asecondary shape that is different from its primary shape and wherein theexpansile element is sufficiently flexible in a normal untreated stateto conform with the secondary shape of the carrier.

In another embodiment, a vaso-occlusive device includes a carrier and anexpansile element wherein the expansile element is fixed to the carrierin a manner such that the expansile element is in a stretched statealong the carrier.

In another embodiment, a vaso-occlusive device includes a carrier havinga plurality of gaps along the carrier and an expansile elementpositioned along an inside envelope of the carrier and wherein theexpansion of the expansile element is controlled such that the expansileelement expands into the gaps but not beyond the external envelope ofthe carrier.

In another embodiment, a vaso-occlusive device includes a carrier memberand an expansile element wherein the expansile element is comprised ofmultiple strands extending along the carrier.

In another embodiment, a vaso-occlusive device includes a carrier and anexpansile member wherein the carrier is a non-coiled cylindricallyshaped structure and wherein said expansile member is disposed insidesaid carrier.

In another embodiment, a vaso-occlusive device includes a carrier and anexpansile member and a stretch resistant member; said expansile memberand said stretch resistant member being disposed in an internal regionof the carrier and wherein the stretch resistant member is in tension onsaid carrier.

The invention disclosed herein also includes a method of treating alesion within a body. The method comprises providing a vaso-occlusivedevice comprising a carrier member and an expansile element wherein thecarrier member is formed into a secondary configuration that isapproximately the same diameter as the lesion and inserting thevaso-occlusive device into the lesion.

Although preferred embodiments of the invention have been described inthis specification and the accompanying drawings, it will be appreciatedthat a number of variations and modifications may suggest themselves tothose skilled in the pertinent arts. Thus, the scope of the presentinvention is not limited to the specific embodiments and examplesdescribed herein, but should be deemed to encompass alternativeembodiments and equivalents.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” Accordingly,unless indicated to the contrary, the numerical parameters set forth inthe specification and attached claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent invention. At the very least, and not as an attempt to limit theapplication of the doctrine of equivalents to the scope of the claims,each numerical parameter should at least be construed in light of thenumber of reported significant digits and by applying ordinary roundingtechniques. Notwithstanding that the numerical ranges and parameterssetting forth the broad scope of the invention are approximations, thenumerical values set forth in the specific examples are reported asprecisely as possible. Any numerical value, however, inherently containscertain errors necessarily resulting from the standard deviation foundin their respective testing measurements.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the invention (especially in the context of the followingclaims) are to be construed to cover both the singular and the plural,unless otherwise indicated herein or clearly contradicted by context.Recitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g., “such as”) provided herein isintended merely to better illuminate the invention and does not pose alimitation on the scope of the invention otherwise claimed. No languagein the specification should be construed as indicating any non-claimedelement essential to the practice of the invention.

Groupings of alternative elements or embodiments of the inventiondisclosed herein are not to be construed as limitations. Each groupmember may be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. It isanticipated that one or more members of a group may be included in, ordeleted from, a group for reasons of convenience and/or patentability.When any such inclusion or deletion occurs, the specification is deemedto contain the group as modified thus fulfilling the written descriptionof all Markush groups used in the appended claims.

Certain embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention. Ofcourse, variations on these described embodiments will become apparentto those of ordinary skill in the art upon reading the foregoingdescription. The inventor expects skilled artisans to employ suchvariations as appropriate, and the inventors intend for the invention tobe practiced otherwise than specifically described herein. Accordingly,this invention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

Furthermore, numerous references have been made to patents and printedpublications throughout this specification. Each of the above-citedreferences and printed publications are individually incorporated hereinby reference in their entirety.

In closing, it is to be understood that the embodiments of the inventiondisclosed herein are illustrative of the principles of the presentinvention. Other modifications that may be employed are within the scopeof the invention. Thus, by way of example, but not of limitation,alternative configurations of the present invention may be utilized inaccordance with the teachings herein. Accordingly, the present inventionis not limited to that precisely as shown and described.

We claim:
 1. An occlusion device comprising: an elongated, expansileelement having a solid mass, that is flexible in an untreated state,consisting essentially of a poly(ethylene glycol) macromer and a pHsensitive monomer; and a carrier element comprising a plurality of loopsforming a helical shape disposed around the expansile element, whereinthe plurality of loops are spaced to form at least one gap and the atleast one gap is between about 0.00025 inches and about 0.2 inches. 2.The occlusion device of claim 1, wherein the carrier element is betweenabout 0.005 inches and about 0.035 inches in diameter.
 3. The occlusiondevice of claim 1, wherein the carrier element is between about 0.0005inches and about 0.01 inches in diameter.
 4. The occlusion device ofclaim 1, wherein the carrier element is between about 0.008 inches andabout 0.016 inches in diameter.
 5. The occlusion device of claim 1,wherein the carrier element is between about 0.00075 inches and about0.004 inches in diameter.
 6. The occlusion device of claim 1, whereinthe expansile element is between about 0.001 inches and about 0.03inches in diameter before expansion.
 7. The occlusion device of claim 1,wherein the expansile element is between about 0.002 inches and about0.25 inches in diameter after expansion.
 8. The occlusion device ofclaim 1, wherein the pH sensitive monomer is sodium acrylate.
 9. Theocclusion device of claim 1, wherein the expansile element is secured tothe carrier element in a stretched configuration that is between about125% and about 600% of its initial length.
 10. The occlusion device ofclaim 1, wherein at least one gap is configured to allow the expansileelement to expand through the at least one gap.
 11. The occlusion deviceof claim 1, wherein the at least one gap has a distance of about 0.00025inches to about 0.005 inches.
 12. The occlusion device of claim 1,wherein the at least one gap is about 0.0013 inches.
 13. The occlusiondevice of claim 1, wherein the carrier element is formed of a materialincluding polyimide, nylon, polyester, polyglycolic acid, polylacticacid, PEEK, Teflon, carbon fiber or pyrolytic carbon, silicone,platinum, steel, tungsten, Nitinol, tantalum, titanium, orchromium-cobalt alloy.
 14. The occlusion device of claim 1, wherein thecarrier element is formed of platinum.
 15. The occlusion device of claim1, wherein the carrier element is formed of tungsten.
 16. The occlusiondevice of claim 1, further including a stretch resistant member.
 17. Theocclusion device of claim 1, wherein the stretch resistant member isformed of a material including steel, nickel titanium, PET, PEEK, nylon,polytetrafluoroethylene, polyethylene, polyolefin, polyolefin elastomer,polypropylene, polylactic acid, or polyglycolic acid.
 18. The occlusiondevice of claim 1, wherein the stretch resistant member is formed ofPET.
 19. The occlusion device of claim 1, wherein the stretch resistantmember is formed of polyethylene.